New Insights into HIV Latency: Identifying Roadblocks to a Cure

Jeffrey Laurence, M.D.

January 17, 2008—Viral latency, the principal barrier to eradicating HIV, is the ability of HIV to lie dormant in very small numbers of long-lived cells, invisible to the immune system and resistant to the effects of current antiretroviral drugs. Last May, amfAR grantee Dr. Suzanne Crowe, working with amfAR fellows Drs. Ya-Lin Chiu and Secondo Sonza in Melbourne, Australia, announced that they had identified a new cellular hiding place for latent HIV: the CD16-positive monocyte (click here to read more). Now, amfAR fellow Dr. Miranda Xhilaga and grantee Dr. Sharon Lewin, working at the Infectious Diseases Unit at the Alfred Hospital in Melbourne, have described a new pathway to the major source of latent HIV: the CD4+ memory T cell.

The memory T cell is critical to the body’s defense against attack by microbes and cancer cells. Writing in the December 2007 issue of the medical journal Blood, Xhilaga, Lewin, and colleagues report that resting memory T cells can be efficiently infected by HIV, and that the virus can remain dormant in them for long periods of time. This ability to infect resting cells is made possible by CCR7—a special molecule on the surface of these cells—and two immune hormones or chemokines that interact with CCR7: CCL19 and CCL21. CCR7 belongs to the same family of chemokine cell co-receptors as CCR5 and CXCR4—the two crucial co-receptors for HIV entry into activated cells.

Normally, CCR7 acts in concert with CCL19 and CCL21 to facilitate the exit of central memory T cells from lymph tissues to sites of inflammation. CCR7 also plays a role in the growth of the dendritic cell, an immune cell that can harbor HIV and transmit it to T cells. Lewin’s lab uncovered a unique mechanism for the establishment of latency, in which CCL19 and CCL21, acting via CCR7, facilitate the infection of resting cells with HIV.

This discovery of a previously unknown mechanism for infecting latent cells will give researchers an important new model for studying HIV latency in the test tube. It also permits the development and evaluation of drugs and chemokine inhibitors that might interfere with this infection process, bringing us another step closer to unraveling the mystery of HIV latency and, perhaps, to a cure.